BACKGROUND: Anti-topoisomerase I antibodies (anti-topo-I) have been known to be a specific serologic marker for systemic sclerosis (SSc). However, anti-topo-I have also been detected fre-quently in the sera of patients with diagnosis other than SSc since the enzyme linked immunosor-bent assay (ELISA) has been used widely. In order to clarify the clinical significance of anti-topo-I on ELISA, we analyzed the clinical features of the patients positive for anti-topo-I. METHODS: Anti-topo-I and other antinuclear antibodies (ANA) were investigated by conventional ELISA methods. The clinical characteristics were analyzed in 38 patients positive for anti-topo-I and 28 patients with SLE but negative for anti-topo-I. RESULTS: Of 38 patients positive for anti-topo-I, 15 were SLE and eight SSc. The mean level of anti-topo-I in the patients with SSc was higher than that in the patients with SLE (P=0.015). Of 15 anti-topo-I positive patients with SLE, 14 had one or more other ANAs in their sera whereas only one of eight anti-topo-I positive patients with SSc did (P=0.000). There was no significant difference in clinical characteristics between anti-topo-I positive and negative patients with SLE. The preva-lences of restrictive lung disease in both groups with SLE were significantly lower than that in the anti-topo-I positive patients with SSc (P=0.008). CONCLUSIONS: Anti-topo-I is not exclusively specific for SSc and present in a considerable subset of SLE. As well as the level of anti-topo-I, the coexistence of other ANAs is helpful to discriminate SLE from SSc. The Anti-topo-I detected by ELISA does not seem to be a risk factor for restrictive lung disease in the patients with SLE, unlike those with SSc.